It is certainly appropriate at this time to recall some of the history that lead to the development of the concept of immune regulation/ suppression. Shortly after the term helper T cells was coined to described lymphocytes that “helped” both humoral and cell-mediated responses, studies from the laboratory of the late Professor Richard Gershon demonstrated that under certain conditions, antigen recognition by T lymphocytes also resulted in the development of cells that are able to suppress immune responses.
Unfortunately, research in this field rapidly shifted from studies of the function of the suppressor T cells to studies of their soluble products that were thought to be shed or secreted T cell receptors. A number of highly complex suppressor cell pathways and cell circuits were developed and were the subjects of more than 5,000 papers during this era. In 1983–1984, this field completely collapsed as studies called into question the existence of the I-J region of the mouse major histocompatibility complex that was thought to encode one of the major chains of the suppressor T cell factors.
The cloning of the T cell receptor at that time firmly established that the T cell receptor genes were completely unrelated to the genes encoding immunoglobulin heavy chains calling into question the existence of soluble T cell factors that contained immunoglobulin VH gene products.
The number of papers in the literature dealing with suppressor cells fell from a high of 1,300–1,500/year in 1981 to 150–200/year by the end of the 1980s. At this point in time, most immunologists felt it was even inappropriate to use the term suppressor cell! Although a number of workers in the period of 1970–1995 continued to focus their studies on T suppressor cells rather than soluble factors, their work was largely ignored by the immunologic community.
The detailed history of their pioneering work will be covered in Chapter 1 by Professor Sakaguchi. Immunologists are somewhat obsessed with dividing what initially appears to be homogeneous population of cells, e.g, CD4+ T lymphocytes, into multiple subpopulations with distinct functional properties, e.g, Th1 and Th2 cells. Ideally, most immunologists desire that each subpopulation could easily be identified and separated by the expression of a cell surface antigen unique to that subpopulation.